title: Oxytocin attenuates NADPH-dependent superoxide activity and IL-6 secretion in macrophages and vascular cells.
abstract: Oxytocin is synthesized and released in the heart and vasculature, tissues that also express oxytocin receptors. Although it has been established this intrinsic cardiovascular oxytocin system is important in normal homeostatic cardiac and vascular regulation, a role for this system in cardiovascular pathophysiology has not been investigated. The current study examined the influence of oxytocin on mechanisms in atherogenesis, oxidative stress, and inflammation in cultured human vascular cells, THP-1 monocytes, and macrophages. Oxytocin receptor protein and mRNA expression, NADPH-dependent superoxide activity, and interleukin-6 secretion were measured. Results demonstrated oxytocin receptor protein and mRNA in THP-1 monocytes and macrophages. Incubation of cells at physiological levels of oxytocin significantly decreased basal and stimulated NADPH-dependent superoxide activity in vascular cells, monocytes, and macrophages by 24-48%. Oxytocin also attenuated interleukin-6 secretion from stimulated THP-1 macrophages and endothelial cells by 56 and 26%, respectively. These findings suggest that oxytocin attenuates vascular oxidative stress and inflammation, two important pathophysiological processes in atherosclerosis. The fact that oxytocin receptors are found in monocytes and macrophages, and oxytocin decreases both superoxide production and release of a proinflammatory cytokine from these cells, suggests a potentially larger role for oxytocin in the attenuation of disease.
authors.affiliation: Dept. of Psychology, Univ. of Miami, Coral Gables, FL 33124, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Szeto
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nation
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.forename: Juan
authors.initials: J
authors.lastname: Dominguez-Bendala
authors.forename: Larry G
authors.initials: LG
authors.lastname: Brooks
authors.forename: Neil
authors.initials: N
authors.lastname: Schneiderman
authors.forename: Philip M
authors.initials: PM
authors.lastname: McCabe
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009249:NADP / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D018045:Receptors, Oxytocin / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D018045:Receptors, Oxytocin; D013481:Superoxides; D010121:Oxytocin; D009249:NADP; D019255:NADPH Oxidases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3